Key information relevant to the recruitment process for the
overall study, such as dates of the recruitment period and locations

Patients were recruited from study sites in the United States and Argentina. There were 10 patients from Argentina.

Pre-Assignment Details

Significant events and approaches for the overall study
following participant enrollment, but prior to group assignment

No text entered.

Reporting Groups

Description

Ranibizumab 0.3 mg

Patients received ranibizumab 0.3 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months.

Ranibizumab 0.5 mg

Patients received ranibizumab 0.5 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months.

Sham Injection/Ranibizumab 0.5 mg

Patients received a sham intravitreal injection monthly for 24 months. Patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months.

Participant Flow for 3 periods

Period 1: Core Study

Ranibizumab 0.3 mg

Ranibizumab 0.5 mg

Sham Injection/Ranibizumab 0.5 mg

STARTED

125

125

127

COMPLETED

98

100

86

NOT COMPLETED

27

25

41

Adverse Event

4

4

1

Death

6

4

4

Lost to Follow-up

5

5

10

Physician Decision

2

1

3

Subject Non-compliance

1

2

1

Subject Required Other Therapy

0

1

3

Subject's Decision

9

8

19

Period 2: Open-label Extension Through Month 48

Ranibizumab 0.3 mg

Ranibizumab 0.5 mg

Sham Injection/Ranibizumab 0.5 mg

STARTED

89
[1]

79
[1]

77
[1]

COMPLETED

63

59

50

NOT COMPLETED

26

20

27

Adverse Event

0

0

2

Death

2

0

0

Lost to Follow-up

1

0

2

Physician's Decision

2

1

3

Subject's Decision

1

3

3

Sponsor’s Decision to Terminate Study

18

15

16

Subject Non-compliance

2

1

0

Subject Required Other Therapy

0

0

1

[1]

Not all participants who completed the core study entered the optional open-label extension.

Period 3: Open-label Extension Through Month 60

Ranibizumab 0.3 mg

Ranibizumab 0.5 mg

Sham Injection/Ranibizumab 0.5 mg

STARTED

89
[1]

79
[1]

77
[1]

COMPLETED

1

1

0

NOT COMPLETED

88

78

77

Adverse Event

0

0

2

Death

2

2

1

Lost to Follow-up

3

0

4

Physician's Decision

2

1

3

Subject's Decision

1

3

4

Sponsor’s Decision to Terminate Study

77

71

62

Subject Non-compliance

2

1

0

Subject Required Other Therapy

1

0

1

[1]

Not all participants who completed the core study entered the optional open-label extension.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

The Baseline Characteristics of the patients enrolled in the open-label extension phase (N=88, 83, 84 patients originally randomized to the ranibizumab 0.3 mg, ranibizumab 0.5 mg, and sham injection groups, respectively) were similar to the Baseline Characteristics of the patients enrolled in the core study.

Reporting Groups

Description

Ranibizumab 0.3 mg

Patients randomized to this group received ranibizumab 0.3 mg monthly administered intravitreally for 24 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months.

Ranibizumab 0.5 mg

Patients randomized to this group received ranibizumab 0.5 mg monthly administered intravitreally for 24 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months.

Sham Injection

Patients randomized to this group received a sham intravitreal injection monthly for 24 months.

Mean Number of Macular Laser Treatments From Baseline Through Months 24 and 36

Measure Description

The need for macular laser treatment was evaluated by the masked (evaluating) physician. Macular laser was administered per protocol-specified objective and subjective criteria starting at Month 3.

Time Frame

Baseline to Month 36

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Intent-to-treat population: All randomized patients, whether or not treatment was received. Missing data were imputed using the last observation carried forward method.

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. For 24-month outcome measures, data in this column represents efficacy data at Month 24.

Sham Injection/Ranibizumab 0.5 mg

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. Although still masked, patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. For 36-month outcome measures, data in this column represents efficacy data at Month 36.

Statistical Analysis 1 for Mean Number of Macular Laser Treatments From Baseline Through Months 24 and 36

Groups [1]

Ranibizumab 0.3 mg vs. Sham Injection

Method [2]

ANOVA

P Value [3]

<0.0001

Mean Difference (Final Values) [4]

-1.0

95% Confidence Interval

-1.4 to -0.7

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

No text entered.

Statistical Analysis 2 for Mean Number of Macular Laser Treatments From Baseline Through Months 24 and 36

Groups [1]

Ranibizumab 0.5 mg vs. Sham Injection

Method [2]

ANOVA

P Value [3]

<0.0001

Mean Difference (Final Values) [4]

-1.1

95% Confidence Interval

-1.5 to -0.7

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

No text entered.

10. Secondary:

Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Months 36 and 48 [ Time Frame: Baseline to Month 48 ]